Butyl-Chloral Hydras

A few general precautions in respect to dispensing butyl-chloral hydrate in solution have already been noted (page 65). The chief difficulty with this substance is its tendency to form water-insoluble oily-like compounds especially with alcohol, as exemplified in the following prescriptions:

The writer of No. I. prescription directed that the butyl-chloral hydrate and the quinine sulphate should be rubbed together, the spirit added to dissolve, then the water. The spirit simply makes the alkaloid and chloral an oily mass, which apparently is not at all affected by water, Apart from the effect which alkaloids have on butyl-chloral hydrate (of which examples follow) alcohol converts it into butyl-chloral alcohol-ate, a compound which is practically insoluble in water. Dispensing-solutions of the hydrate are sometimes made with a mixture of rectified spirit and glycerin, which on keeping for a few days are quite immiscible with water, and on pouring a little of such solutions into water butyl-chloral alcoholate sinks to the bottom in oily drops. Alcohol as a solvent for the hydrate should be avoided. The British Pharmacopoeia states that the hydrate 'is soluble in about 50 parts of water, and in its own weight of glycerin or of alcohol': it would be advisable for the B.P. to add that in alcoholic solution it is changed to an insoluble substance.

The best dispensing-solution is made by dissolving 1 ounce of the hydrate in 2 1/2 fluid ounces of glycerin and 1 ounce of boiling water, and when cold making 4 fluid ounces of the solution with water, In making aqueous solutions care should be taken not to heat above 1700 F, otherwise the hydrate fuses and an opalescent mixture results. No. II. prescription typifies the best method of compounding. Heat the glycerin in a test-tube by dipping the tube in a small basin of boiling water for a few minutes, add the butyl-chloral hydrate, and dissolve. Half fill a 6-ounce bottle with chloroform-water, pour the glycerin solution into it and shake, wash the test-tube with 1 ounce of chloroform-water and add to the bottle, add the tincture, and make up. Reference has been made to the influence of alkaloids upon the hydrate. The following are good examples:

No. III. dispensed as written (the butyl-chloral hydrate solution being added to the citrate solution) gave a thick, sticky precipitate. A clear mixture was obtained by first dissolving the hydrate in \ ounce of glycerin and half as much water gently heated, adding the solution to the rest of the ingredients previously mixed and dissolved. An oily deposit forms in No. IV. when either the antipyrin or butyl-chloral hydrate is added to the rest of the ingredients in the prescription. These two ingredients are incompatible (as chloral hydrate and antipyrin are, page 97), and some addition or omission is necessary to make a clear mixture. The following modification does this:(a) Dissolve the quinine in 2 ounces of water acidulated with 40 drops of dilute hydrochloric acid; (b) dissolve the antipyrin and bromide in the same quantity of water; (c) dissolve the butyl-chloral hydrate in a mixture of spt. chlorof. 3j. and S.V.R. 3j.(or spt. chlorof. 3ij.) and make up to 2 ounces with water. Mix a, b, and c; an oily deposition of butyl-chloral antipyrin immediately takes place, which, after a few hours, with an occasional shake dissolves, forming a clear mixture.

Caffeinae Citras sometimes gives trouble owing to its loose combination, water sufficing to split it up, partly or wholly, into caffeine and citric acid, both of which dissolve as such. The following show what may happen:

No. I. dispensed as written becomes, after a brisk shake, solid in two minutes. If solutions of the citrate and salicylate are mixed without shaking and left undisturbed, the growth of crystallisation may be observed proceeding with great beauty. This is due to the free citric acid combining with the alkali of the sodium salicylate, thus setting salicylic acid free. Sodio-caffeine salicylate is the most soluble compound of caffeine, and is formed by dissolving caffeine in sodium-salicylate solution; advantage should, therefore, be taken of this fact by dispensing No. I. with an equivalent of caffeine in place of the citrate- that is, half the amount. It is worthy of note that double the quantity of sodium salicylate gives a clear mixture with the caffeine citrate, and this is also obtained by the use of a drachm of sodium citrate, so that in gouty or rheumatic cases, where the citric acid is advantageous, therefore required, either of these expedients may be resorted to. No. II. mixture crystallises after standing a short time, although sodium salicylate is present in greater proportion than that necessary for perfect solution. By mixing the ingredients in the order written, considerable precipitation of crystals takes place a few seconds after the phenazone is added.

When the mixture is warmed, the crystals dissolve, but separate again after several hours. When the order of mixing is changed- as, for example, (i) sodium salicylate, caffeine citrate, phenazone ; (2) caffeine citrate, phenazone, sodium salicylate ; (3) phenazone, sodium salicylate, caffeine citrate- different results are obtained. No. 1 immediately gives crystals, Nos. 2 and 3 remain clear for many hours, but the crystals formed are not like those in No. 1, which are phenazone-like, but are nearly 1/2 inch long. All the crystals are soluble in a small quantity of water, and give with ferric chloride the characteristic colour given by that salt when added to a mixture of phenazone and a salicylate. In order to compound the mixture clear, the caffeine citrate should be neutralised with ammonia. A mixture thus made remains clear, but the use of half the amount of caffeine has the same effect. This is further illustrated in the next two prescriptions, where the inorganic salts have some influence on precipitation in b :

In the case of the next prescription, if the first two ingredients are put into a bottle and the infusion added, a thick precipitate is formed. A clear solution is obtained by dissolving the potassium citrate in half the infusion and the caffeine citrate in the other half, and adding the latter to the former. If the order of mixing is reversed, precipitation takes place.

Caffeine per se is more soluble in water (1 in 80, compare page 42) than alkaloids generally are, consequently there is less fear of it being precipitated from its salts by alkalies, as the following shows:

Here the proportion of caffeine to solvent is about 1 to 200, or much in excess of the proportion for complete solution.